Ibrahim Malami

Induction of Haemolysis and DNA Fragmentation in a Normal and Malarial-Infected Blood by Commonly - used Antimalarial Drugs in the North-Western Region of Nigeria.

BACKGROUND Antimalarial drugs are medicines that are used to prevent or treat malaria effectively at different stages in the life cycle of the malarial parasites. In spite of this, a good number of these drugs have the potential to cause harm when they are misused or abused. OBJECTIVE This study was undertaken to evaluate the effects of commonly-used antimalarial drugs in the North Western region of Nigeria on haemolysis and DNA fragmentation in the blood of normal and malarial infected humans ex vivo. METHOD The drugs used were artemisinine, artesunate, chloroquine, coartem and quinine (0.5-8.0 mg/ml). Haemolysis, haemoglobin status and DNA fragmentations were assayed for using standard procedures. RESULTS It was observed that all the drugs induced a remarkable dose-dependent haemolysis with more pronounced effects on apparently healthy humans. There was a significant (P < 0.05) decrease in the level of haemoglobin in normal blood samples when compared with control samples. Contrariwise, in the malaria-infected blood, the haemoglobin level significantly (P < 0.05) increased as compared with control. The drugs caused an exceptional significant (P < 0.05) induction of DNA fragmentation when compared with control. CONCLUSION Commonly-used antimalarial drugs induced haemolysis and altered haemoglobin status which may spontaneously increases the cellular iron levels; a substrate for Fenton and Haber Weiss reactions, and eventually induces DNA fragmentation. Hence, adequate care should be taken during prescription with total avoidance for self medications and/or drugs abuse as a result of their adverse effects within the red blood cells and its immediate microenvironment.

Alteration of redox status by commonly used antimalarial drugs in the north-western region of Nigeria

This study was designed to investigate the alteration of redox status by commonly used antimalarials in Nigeria. Drugs used were artemisinin, artesunate, chloroquine, coartem and quinine at the final concentrations of 0.5–8.0 mg/mL. Blood samples were collected from malarial patients and apparently healthy humans for comparison. Reduced glutathione, catalase, superoxide dismutase (SOD) activities, protein content and lipid peroxidation were determined. All drugs significantly (p < 0.05) increases the protein level relative to control in normal blood, whereas in the infected, a significant (p < 0.05) reduction was observed. In normal blood, the antimalarials dose dependently decreased (p < 0.05) SOD and catalase activities with significant (p < 0.05) increase in the infected. The level of glutathione in normal blood significantly (p < 0.05) increases as compared with control, whereas in the infected, similar observation was made except that the levels were less, relative to control sample. Malondialdehyde level significantly (p < 0.05) increases with increase in drugs concentration even though less than the level in the control with few exceptions. These effects were dose dependent and more pronounced in non-malarial conditions. Commonly used antimalarials might alter the redox status in both healthy and non-healthy subjects thereby inducing oxidative stress.

Spices with Breast Cancer Chemopreventive and Therapeutic Potentials: A Functional Foods Based-Review

BACKGROUND Cancer is a multifaceted metabolic disease that affects sizeable dwellers of rural and urban areas. Among the various types of cancer, mammary cancer is one of the most frequently diagnosed cancers in women. Its menace can be curbed with locally consumed spices due to their multiple bioactive phytochemicals. AIMS This review focuses on the breast cancer chemopreventive and therapeutic potentials of locally consumed spices. METHODS/RESULTS The most commonly consumed spices with breast cancer chemopreventive and chemotherapeutic phytochemical include pepper, onions, ginger, garlic, curry and thyme containing many biologically active metabolites ranging from vitamins, fatty acids esters, polyphenols/phenolics, sulfurcontaining compounds and anthraquinones with proven antioxidant, anti-inflammatory, immuno-modulatory, antitumor and anticancer properties against breast cancer/carcinogenesis. Therefore, extracts and active principles of these spices could be explored in breast cancer chemoprevention and possibly therapeutically which may provide an avenue for reducing the risk and prevalence of breast cancer.

Synthesis and antibacterial evaluation of 3-Farnesyl-2-hydroxybenzoic acid from Piper multiplinervium.

3-Farnesyl-2-hydroxybenzoic acid is an antibacterial agent isolated from the leaves of Piper multiplinervium. This compound has activity against both Gram positive and Gram negative bacteria including Escherichia coli, Staphylococcus aureus and Helicobacter pylori. This research aimed to synthesize a natural antibacterial compound and its analogs. The synthesis of 3-Farnesyl-2-hydroxybenzoic acid consists of three steps: straightforward synthesis involving protection of phenolic hydroxyl group, coupling of suitable isoprenyl chain to the protected aromatic ring at ortho position followed by carboxylation with concomitant deprotection to give the derivatives of the salicylic acid. All the three prenylated compounds synthesized were found to exhibit spectrum of activity against S. aureus (ATCC) having MIC: 5.84×10(-3), 41.46×10(-2) and 6.19×10(-1) μmol/ml respectively. The compounds also displayed activity against resistance strain of S. aureus (SA1119B) having MIC: 5.84×10(-3), 7.29×10(-3) and 3.09×10(-1) μmol/ml respectively. This synthesis has been achieved and accomplished with the confirmation of it structure to that of the original natural product, thus producing the first synthesis of the natural product and providing the first synthesis of its analogs with 3-Farnesyl-2-hydroxybenzoic acid having biological activity higher than that of the original natural product.

Postmenopausal osteoporosis and breast cancer: The biochemical links and beneficial effects of functional foods

Breast cancer as a multifactorial disease has been classified among the major causes of morbidity and mortality in women across the world, with a higher prevalence among post-menopausal women. Osteoporosis, a condition characterized by altered bone mineralization is also commonly found among post-menopausal women. Consequently, post-menopausal women are at risk of morbidity and mortality associated with breast cancer and postmenopausal osteoporosis. This may not be unconnected to the fact that, there may be existent biochemical links between the two mayhems, which might rally round between the cellular and molecular connectivity based on the actions and inactions of RANKL, estrogen, free radicals-induced oxidative stress and metabolic implications of age related obesity among others. Cells and tissues including breast and bone are more prone to oxidative stress with age, and oxidative stress could alter the activity of key proteins and pathways required for protection against breast cancer and osteoporosis. As a result, the potentials of antioxidant rich functional foods in preventing, managing and possibly treating breast cancer and postmenopausal osteoporosis cannot be overemphasised. This review mainly uses ISI, SCOPUS and PubMed indexed journals and books containing various experimental reports vacillating from humans, animals and in vitro studies in relation to breast cancer and postmenopausal osteoporosis, biochemical links and possible beneficial effects of functional foods. One distinct feature of the review is that it categorically intends to provide a critical appraisal on the said available experimental data within the variables of breast cancer and osteoporosis among females vis-à-vis the potentials of functional foods.

A review on the ethnomedicinal uses, phytochemistry and pharmacology of Alpinia officinarum Hance

ETHNOPHARMACOLOGICAL RELEVANCE Alpinia officinarum Hance is a perennial plant that has been traditionally used for many decades to treat several ailments including inflammation, pain, stomach-ache, cold, amongst others. Pharmacological studies over the years have demonstrated remarkable bioactivities that could be further explored for development of new therapeutic agents against various ailments. AIM OF THE STUDY The paper critically reviewed the ethno-medicinal uses, pharmacology, and phytochemistry of A. officinarum. METHODS Keywords including A. officinarum and its synonyms were searched using electronic databases including ISI web of knowledge, Science direct, Scopus, PubMed, Google scholar and relevant database for Masters and Doctoral theses. RESULTS A. officinarum is prepared in Asia, Turkey, Morocco and Iran as a decoction, infusion or juice as a single preparation or in combination with other herbs, food or drinks for the treatment of general health problems including cold, inflammation, digestive disorders, etc. Pharmacological studies revealed the potent in vitro and in vivo bioactivities of various parts of A. officinarum that include anti-inflammatory, cytotoxicity, homeostasis, lipid regulation, antioxidant, antiviral, antimicrobial, antiosteoporosis, etc. Over 90 phytochemical constituents have been identified and isolated from A. officinarum comprising vastly of phenolic compounds especially diarylheptanoids isolated from the rhizome and considered the most active bioactive components. CONCLUSION In vitro and in vivo studies have confirmed the potency of A. officinarum. However, further studies are required to establish the mechanisms mediating its bioactivities in relation to the medicinal uses as well as investigating any potential toxicity for future clinical studies.

Response to the letter to the editor on the article ‘Alteration of redox status by commonly used antimalarial drugs in the north-western region of Nigeria’ by Karolina et al.

It is worthy to mention that oxidative stress is a common pathogenic mechanism underlying the development of many diseases and conditions including malarial infection where both the host and the parasite are affected. Although oxidative stress, anaemia and malarial infection are closely linked, their complex relationships and the functional relevance of oxidative stress genes are poorly understood. In Africa, the first line of therapy for the treatment of malaria is usually through the administration of antimalarial drugs. At present, the commonly used antimalarial drugs in Nigeria are artemisinin, artesunate, chloroquine, coartem and quinine with different mechanism of actions at the therapeutic doses. In spite of this, a good number of these drugs have the potential to cause harm when they are misused or abused. It is important to appreciate the facts that these drugs, when administered, are basically transported via blood stream and therefore can affect various blood components like erythrocytes, monocytes, neutrophils, among others. Therefore, it is safe to postulate that whole blood cells are the first line of contact and a major systemic reservoir of these xenobiotics. Our published work ‘Alteration of redox status by commonly used antimalarial drugs in the northwestern region of Nigeria’ is actually a preliminary work and a part of larger scope of our research intended to focus on the ‘effects of overdose/misuse of commonly used antimalarial drugs on specific blood cells components’ using in vitro and in vivo models. You will of course agree with us that it is more rational for a good scientist to initially commence such a research with the entire blood system in order to have a good picture and direction on the appropriate line of research, including cell types, to pursue with a view to answer our broad research question. Thus, the (high) concentration of the drugs was selected because the research was aimed at deciphering the biochemical implications of the overdose/ abuse of antimalarials in relation to redox status. Hence, the selected concentrations may not necessarily reflect the final in vivo concentrations of the drugs when administered at the therapeutic doses.

Modulatory role of rutin on 2,5-hexanedione-induced chromosomal and DNA damage in rats: validation of computational predictions

Abstract The aim of this study was to evaluate the potentials of rutin on 2,5-hexanedione-induced toxicities. Two successive phases were involved using in silico and in vivo approaches. The in silico was adopted for potential oral toxicity and docking. The in vivo was carried-out in two stages for two weeks; the ameliorative (stage 1, first week), preventive, and curative studies (stage 2, extended to second week). In stage 1, rats were divided into four groups of seven each (distilled water, 3% (v/v) 2,5-hexanedione, 10 mg/kg rutin, and co-administration). In stage 2, the experimental groups were given either rutin or 2,5-hexanedione and treated in reverse order. Lipid peroxidation, protein carbonyl, and DNA fragmentation in tissues and bone marrow cells micronucleus were determined. The predicted Median lethal dose (LD50) of >5000 mg/kg and toxicity class of five (5) indicates the safety of rutin when orally administered. 2,5-Hexanedione comfortably docked in to the active sites of SOD (−22.857Kcal/mol; KI = 0.9621 µM), GPx (−11.2032Kcal/mol; KI = 0.9813 µM), and CAT (−16.446Kcal/mol; KI = 0.9726 µM) with strong hydrogen bond and hydrophobic interactions. However, only strong hydrophobic interaction was observed in the case of DNA (−3.3296Kcal/mol; KI = 0.9944). In vivo findings revealed deleterious effects of 2,5-hexanedione through induction of oxidative and chromosomal/DNA damage characterized by higher level of malondialdehyde, micronuclei formations, and DNA fragmentation. These have invariably, validates the findings from in silico experiments. Furthermore, rutin was able to ameliorate, protect, and reverse these effects, and was relatively non-toxic corroborating toxicity predictions. Rutin exhibited counteractive effects on 2,5-hexanedione-induced oxidative, chromosomal, and DNA damage.